In the prior art regarding assembly and bonding of multilayer polymer or hybrid articles that consist of polymers and inorganic materials, there is a problem with bonding the individual layers at a low temperature and solvent free conditions. The problems of bonding such articles are compounded by incorporating patterns on one or more of the layers since liquids, such as glue, tend to wick into cavities, altering the desired geometries.
In the prior art regarding polymer articles there is a problem with binding to a biofunctionalised substrate: Many biosensors require a microfluidic channel layer to distribute, separate or mix the sample before detection and to improve the mass transport of analyte down to the sensor surface. Polymers are the most commonly used material for microfluidics due to its low cost, ease of manufacture and tailorable surfaces. However, bonding a plastic substrate to a biofunctionalised surface remains a problem. Heat, solvents or oxygen plasma treatment, that is often used to activate the surfaces prior to bonding, destroys the biofunctionalization. Moreover, two stiff substrates cannot form a perfect seal and react with each other if they are not perfectly smooth on a molecular level. Clamping of microfluidic devices made from rubberry materials is only possible for simple channel geometries due to deformation of the material under pressure, which may lead to leakage and altered fluidic behavior.
In microfluidic devices with closed channels there is the problem to functionalize the closed micro channels: Surface functionalisation of microfluidic channels is essential for controlling the liquid flow, for preventing unspecific binding of analytes and for attaching biomolecules. Currently used polymers must first be surface activated before functional molecules can be attached. Typically, traditional plasma treatment does not give a homogeneous surface coverage and the density of modifications cannot be controlled. Further, thermoplastics activated via hydrogen abstraction from light activated compounds such as benzophenone suffer from low density surface coverage.
Regarding for instance closed microfluidic systems there is the problem to assemble the microfluidic devices: Microfluidic devices typically consist of several bonded micropatterned polymeric layers. The bonding of these layers can be complicated and require heating, plasma treatment, ultrasonic welding or treatment with solvents.
In the art, off stoichiometry has long been well known and one patent describing thiol-ene polymers (U.S. Pat. No. 3,697,396) claims significantly off-stoichiometric mixtures, 0.5/1 to 2/1 ene to thiol ratio, and gives examples of materials fabricated via significant off stoichiometry and reports curing time and shore hardness of said materials. Single shaped molded cast articles from thiol-enes are claimed, while micropatterning and assembly of articles from separately fabricated thiol-ene pieces are not mentioned.
Off stoichiometric formulations have been previously described in the art. In a work by Khire et al. (Adv. Mater. 2008, 20, 3308-3313), very thin nanopatterned off stochiometry thiol-ene films were fabricated using a nanopatterned PDMS stamp. The prepolymer contained a small excess of thiols and the thiol groups present on the polymer surface after the polymerization was utilized for subsequent surface modification via a grafting-to process. Off stoichiometry was also used to control the thickness of the grafted layer where, by adjusting the thiol to ene ratio, oligomers of a predetermined average size where polymerized in bulk and attached to the thiol excess polymer surface. While off stoichiometric formulations have been known in the art and sometimes are used, no systematic investigation into the properties of off-stoichiometric formulations have been performed. On the contrary, it is often argued that off-stoichiometry results in very poor mechanical properties, and should be avoided, (Belfield et al. ACS symposium series 2003, p 65). The reasons for this are twofold: firstly deviation from stoichiometry results in a non-optimized polymeric network with less than the maximum number of crosslinks and the inclusion of dangling chain ends; and secondly, there is a finite risk that monomers are left unreacted in the network, thus risking leaching into the environment.
Ternary prepolymer formulations have been previously described in the art. Carioscia et al. (J. A. Carioscia et al., Polymer 48, (2007) 1526-1532) described the cure kinetics and Tg of a ternary prepolymer formulation consisting of a thiol an allyl and an epoxy monomer. In the mixture there was also added a radical initiator and anionic initiator. While good ultimate mechanical properties were achieved, no attempt to temporally separate the dual cure events to utilize the inherent reactivity after an initial cure was attempted nor was such a strategy suggested.
For micropatterning of polymers, commercial as well as in-house thiol-ene formulations using both molding and direct photolithography have been described in the art. In (D. Bartolo, et al, Lab Chip, 2008, 8, 274) a method utilizing NOA 81, a commercially available thiol-ene based UV-curable glue, was shown to result in microfluidic devices, with adequate mechanical and bulk materials properties. Also good bonding to a substrate was shown upon renewed polymerization of an oxygen inhibited uncured polymer layer situated on the bottom of the device. Furthermore, it was claimed that oxygen inhibition, due to the high gas permeability of the PDMS mold, was effective for creating a layer of unreacted prepolymer on the channel surfaces, which is useful for subsequent surface modifications. In another example (J. Ashley et al. Lab Chip, 2011, 11, 2772-2778), a freeform UV-curable photolithographic technology using thiol-enes was shown. Uniquely, the propensity for unwanted cure in shadow regions exhibited by thiol-enes, due to the high mobility of radicals and low propensity for inhibition, was hindered by a large amount of inhibitor added to the mixture.
While off stoichiometric formulations have been used in at least one instance for surface modification of nanopatterned materials, no technology describing free standing polymeric structures from off stoichiometric monomer mixtures has been disclosed. The technologies and materials presented above therefore are almost exclusively incompatible which prevents simple process and materials combinations to achieve mass fabrication of micropatterned polymeric articles. While many of these processes may be suitable for the particular purpose which they address, they are not as suitable for cost beneficial fabrication of polymeric micropatterned articles with superior surface modification, facile bonding and easy patternability via molding and/or potolithography.
In these respects, the materials and their fabrication process that enables the fabrication of microfluidic devices with on-board connections between the everyday world to microfluidic channels and minute reaction chambers, durable surface properties that prevent analyte adsorption and robust enclosure of channels according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides microfluidic devices with hitherto unrealized usability and economies of scale.